JPH0149122B2 - - Google Patents

Abstract

This invention relates to topical cosmetic preparations. More particularly, this invention relates to a topical cosmetic preparation for the treatment of oily hair and seborrheic skin which comprises an effective amount of at least one compound of the formula <IMAGE> (I) wherein R1, R2, and R3, any of which may be the same or different, each represent hydrogen, hydroxyl, or -OR4, where R4 is an alkyl of from 1 to 6 carbon atoms or a substituted or unsubstituted benzyl, or two of the groups R1, R2, and R3 represent methylenedioxy; X is a substituted or unsubstituted alkylene of from 1 to 3 carbon atoms; and Y is -COOH, -CN, -CONR5R6, or -COOR7, where R5 and R6 each represent hydrogen, alkyl of from 1 to 6 carbon atoms, or substituted or unsubstituted aryl, or aralkyl, or together with the nitrogen atom R5 and R6 represent a heterocycle, and R7 is an alkyl of from 1 to 6 carbon atoms or a substituted or unsubstituted aralkyl.

Description

[Detailed description of the invention]

The present invention is directed to topical cosmetics used to overcome the greasy and unaesthetic appearance of hair and skin. Excessively strong secretion of the scalp sebaceous glands gives the hair a greasy appearance, which is generally seen as less aesthetically pleasing. Therefore, in order to give the hair its healthy appearance again, efforts have been made to normalize the secretion of the sebaceous glands by means of suitable drugs. A number of synthetic products, in particular sulfur-containing compounds, have already been used to eliminate this seborrheic sign, but it has not been possible to achieve practically satisfactory results in terms of effectiveness or application technical properties. Formula from French Patent No. 2383662 Cosmetics containing oleyl esters are known, in which R ¹ may in particular be a phenyl, benzyl or phenethyl group. This compound is effective against Corynebacterium Acne or against the inflammation, pustules, etc. that occur in acne. Now the general formula: [In the formula, R ₁ , R ₂ and R ₃ are unrelated to each other and mean a hydrogen atom, a hydroxy group, an OR ₄ - group (in the formula, R ₄ represents an alkyl group having 1 to 6 carbon atoms) or R Two of ₁ , R ₂ and R ₃ mean a methylenedioxy group, in which case R ₁ , R ₂ and R ₃ do not mean a hydrogen atom at the same time, and X means that the carbon chain has 1 carbon atom.
~3 alkylene group, Y is CONR ₅ R ₆ or
COOR ₇ (wherein R ₅ and R ₆ are hydrogen atoms, alkyl groups having 1 to 6 carbon atoms, benzyl or 3,4-dimethoxybenzyl groups, and R ₇ is hydrogen atoms having 1 to 6 carbon atoms.
is an alkyl group. ) means. ] or 2-(3,4-dimethoxy-
benzyl)-acetoacetic acid-methyl ester, 4-
(3,4-methylenedioxy-benzyloxy)-
Phenyl acetic acid ethyl ester, N-[β-(3,4
-dimethoxy-phenyl)-ethyl]-3,4-dimethoxy-phenyl-acetamide or N-[β
-(3,4-dimethoxy-phenyl)-ethyl]-
It has been found that topical cosmetic compositions containing N-methyl-3,4-dimethoxy-phenyl-acetamide have particularly noteworthy effectiveness in the treatment of seborrheic skin and highly fatty hair. Ta. The compounds to be used in the cosmetic compositions according to the invention are well known in the literature as such or in the form of precursors and can be purchased in part. Although only the arylalkanoic acids which are the basis of the compounds are purchased, the compounds to be used according to the invention can be prepared in a simple manner using generally known methods of organic chemistry. The corresponding hydroxy compounds can also be obtained from alkoxyarylalkanoic acids by partial or complete demethylation, often using hydrogen iodide. This production method is also applicable to the production of hydroxyarylalkanoic acid amides. Benzyloxy-substituted arylalkanoic acid derivatives are obtained by reaction of optionally substituted benzyl halides with hydroxy-substituted esters. The carboxylic acid function can be changed accordingly in a generally known manner. Alkoxybenzylacetoacetic esters can be prepared by alkylating the corresponding unsubstituted esters with alkoxybenzyl halides. Corresponding esters or amides can be prepared from carboxylic acids by conventional methods of organic chemistry. Examples of the arylalkanoic acids that form the basis of the compounds to be used in the cosmetics according to the invention include 2
-hydroxy-, 3-hydroxy-, 4-hydroxy-, 2-methoxy-, 3-methoxy-, 4-
Methoxy-, 4-ethoxy-, 4-isopropyloxy-, 4-hexyloxy-, 4-benzyloxy-, 4-(3,4-methylene-dioxy-
benzyloxy)-phenylacetic acid, 2-(p-hydroxy-phenyl)-, 3-(p-hydroxy-phenyl)-, 4-(p-hydroxy-phenyl)-
Butyric acid, 4-hydroxy-,3-methoxy-,2,
4-dihydroxy-, 2,5-dihydroxy-,
3,5-dihydroxy-, 3,5-dihydroxy-, 2,4-dimethoxy-, 3,4-dimethoxy-, 3,4-methylenedioxy-, 3-methoxy-4-ethoxy-, 3-methoxy- 4-benzyloxy-,3,4,5-trihydroxy-,3,
4,5-trimethoxy-phenylacetic acid, 2-(3,
4-dimethoxy-benzyl)-,2-(3,4-methylenedioxybenzyl)-acetoacetic acid, 2-(p
-methoxy-phenyl)-2-methyl-,3-
(3,4-dimethoxy-phenyl)-propionic acid may be mentioned. Alcohol components for the production of the arylalkanoic esters to be used according to the invention include, for example, methanol, ethanol, propanol,
2-propanol, butanol, isobutanol, tert-butanol, bentanol, hexanol, benzyl alcohol, 3,4-dimethoxy-
Benzyl alcohol falls under this category. Amine components for the preparation of the hydroxy- or alkoxyarylalkanoamides to be used according to the invention include, for example, ammonia, methyl, ethyl, propyl, butyl, hexyl, dimethyl, diethyl, dipropyl- , dibutyl-, benzyl-, 3,4-dimethoxybenzyl-amine. Cosmetics according to the invention include solutions, gel-like suspensions, emulsions, ointments, pastes, in water, in alcohols, in aqueous-alcoholic mixtures, in oils, of the effective compounds of the general formula to be used. , is an aerosol. In principle, almost all cosmetic applications for skin and hair treatment are suitable for processing the compounds of the general formula mentioned. This is because in that way it imparts anti-seborrheic properties. The cosmetics according to the invention can therefore be present in the form of hair lacquers, waving lotions and hair washes. Such cosmetics contain, in addition to the compound of the above general formula which is present in solution or suspension, surfactants, cellulose derivatives, cationic compounds, vitamins, resins, colorants and perfume oils. The alcoholic or hydroalcoholic solutions can also be mixed with suitable propellant gases and used in the form of aerosols. Other application forms of cosmetics according to the invention are such products that are applied to the skin and are generally present in the form of creams, emulsions, gels, pastas. In addition to the compound of the above general formula, this cosmetic contains water,
solvents, surface-active compounds, oils and fats, waxes, perfume oils,
Contains colorants, preservatives and special active substances. The most customary application form of the cosmetic composition according to the invention for the treatment of highly fatty hair is shampoo. Such shampoos can be realized in their simplest form, consisting of solutions of anionic, cationic, nonionic or amphoteric surfactant compounds in combination with compounds of the general formula above. As anionic surfactants, for example, alkyl sulfates,
Alkyl ether sulfates, alkyl sulfonates, sulfated monoglycerides, sulfonated alkanolamides, monosulfosuccinates of fatty alcohols, condensation products of fatty acids and protein hydrolysates may be included.
Suitable cationic surfactants include, for example, long-chain quaternary ammonium compounds, esters of fatty acids and amino alcohols. Products used as nonionic surfactants in the cosmetic compositions according to the invention include, for example, sugar esters, esters of polyols, condensation products of ethylene oxide and fatty acids, fatty alcohols, long-chain alkylphenols, long-chain amides. should be important. Examples for amphoteric surfactants are petaine derivatives and aminoxides. In addition, the shampoos according to the invention may contain customary cosmetic additives, such as thickening agents, colorants, fragrances, preservatives and special active substances, such as anti-dandruff agents. Suitable thickening agents include fatty acid alkanolamides, carboxymethylcellulose, hydroxymethylcellulose, rubber, and esters of long-chain polyols. The cosmetic product according to the invention contains the arylalkanoic acid derivative in an amount of 0.01 to 20% by weight, preferably 1 to 10% by weight, based on the total cosmetic material. In this case, the remaining ingredients are in the order of quantity customary for such cosmetics.
For example, in the case of shampoo, the ingredients may vary as follows: 4-20% by weight of surfactant, 0.1-5% by weight of thickener, 0.5-2% by weight of fragrance, 0.01-0.1% by weight of colorant,
Preservatives 0.1-0.2% by weight. With the cosmetic composition according to the invention prepared in the form of a shampoo, immediately satisfactory results are achieved with use once a week. In doing so, it is possible to reduce the fatty appearance of the hair and to suppress post-fatty formation during the treatment time, which provides the possibility of normal hair protection. When used in the form of creams, emulsions or gels, regular application to the skin can result in a significant and lasting improvement in its appearance.
Optionally in combination with other acne preparations, it is possible to obtain satisfactory results in the case of acne as well. The following non-limiting examples illustrate the invention in more detail. EXAMPLES First, some arylalkanoic acid derivatives for use in cosmetics according to the invention will be described. (A) 3,4-dihydroxy-phenyl-acetic acid as starting compound for the corresponding ester or amide.
Gesellschaft) Vol. 42, p. 2949. This was done in this case via 3,4-dimethoxyphenylacetic acid, which is obtained as a commercial product. 3,4-dimethoxyphenylacetic acid
115 g (587 mmol), 57% hydriodic acid 1052 g
(2.35 mol) and 14 g of red phosphorus, 95
The mixture was stirred for 1.5 hours at 105-110 DEG C. and for a further 1.5 hours at 105-110 DEG C., during which time the calculated amount of methyl iodide (166.5 g) was distilled off. After cooling the mixture, separating the red phosphorus, concentrating and evaporating the solution and taking up the residue in ether, the ethereal solution was treated with NaHSO ₃ -solution and activated carbon. After drying the light yellow solution over Na ₂ SO ₄ and concentrating and evaporating, the residue is suspended in methylene chloride, the residual water is distilled off azeotropically and, after cooling of the suspension, the solid product is Aspirate and dry at 50°C. 3,4 with a melting point of 126-129℃, which is 64% of the theoretical value
63 g of -dihydroxyphenylacetic acid were obtained. (B) 3,4-dihydroxy-phenyl-acetic acid ethyl ester This compound was obtained by esterification of the free acid with ethanol. n ²⁰ _D = 1.5268 (without distillation) (C) 3,4-dimethoxy-phenyl- as starting compound for the corresponding ester or amide
Acetic acid This compound is a commercial product. Its manufacture is described in Beilstein, volume 10, page 268. (D) 3,4-Dimethoxy-phenyl-acetic acid ethyl ester This compound was obtained by esterification of the free acid with ethanol. Its characteristic values are as follows: Boiling point 112°C/0.13 mbar; n ²⁰ _D = 1.5174. J.Chcm.Soe.
1959, p. 2157. (E) 2-(3,4-dimethoxy-benzyl)-acetoacetic acid-methyl ester This compound was prepared by a known method as indicated in Organikum, 8th edition, page 469.
Obtained by alkylating acetoacetic acid methyl ester with 3,4-dimethoxy-benzyl-chloride. Melting point 51°C (F) 4-Hydroxy-phenylacetic acid-ethyl ester This compound was obtained by esterification of the free acid with ethanol. Boiling point 117°C / 0.14 mbar; n ²⁰ _D = 1.5240 Literature description: J.Org.Chem. vol. 22 (1957) p. 1577 (G) 3-Hydroxy-phenylacetic acid-ethyl ester This compound esterifies the free acid with ethanol. It was obtained by converting Boiling point 111°C / 0.16 mbar; n ²⁰ _D = 1.5236 Literature description: Diss.
Pharm. Pharmacol) Volume 20 (1968) Page 607 (H) 3,4-dimethoxy-phenylacetic acid-diethylamide This compound was obtained by reacting the acid chloride with diethylamine in ether at room temperature. Boiling point 144°C / 0.08 mbar; n ²⁰ _D = 1.5342 Literature description: French patent (Franz, Pat) No. 1336388
Specification (I) 3,4-Dihydroxy-phenylacetic acid-diethylamide This compound was prepared from compound (H) in a yield of 67% according to the method described under (A). Melting point 134-137℃ Literature description: Helv.Chim.Acta volume 45 (1962) 270
Page (J) 3,4-methylenedioxy-phenylacetic acid-
Ethyl ester This compound was obtained by esterifying the free acid with ethanol. Boiling point 103°C / 0.13 mbar: n ²⁰ _D = 1.5198 Document: French Patent No. 1549379 (K) 4-(3,4-methylenedioxy-benzyloxy)-phenylacetic acid-ethyl ester in 100 ml of ethanol In a solution of 2.16 g (94 mmol) of sodium in sodium alcoholate, 4-
Hydroxy-phenylacetic acid ethyl ester 16.9g
(94 mmol) was added with stirring. Continued 3,
4-methylenedioxybenzyl chloride 16.0g
(94 mmol) was added dropwise and the mixture was kept at boiling temperature for 8 hours. After evaporation and concentration, the residue was taken up in ether and washed with Na ₂ CO ₃ solution and water, the ethereal solution was treated with activated charcoal and, after evaporation and concentration, the residue was distilled at 0.13 mbar. By the time the bottom temperature reached 240°C, 5.9 g of easily volatile substances had been distilled off.
21 g of the residue was purified using silicic acid gel (manufactured by Merck, particle size 0.063-0.200) using methylene chloride as an eluent.
mm) column chromatography. melting point
^4- ( _3,4-
16.7 g (57% of theory) of ethyl ester (methylenedioxybenzyloxy)-phenyl acetate were obtained. (L) 3-(3,4-dimethoxy-phenyl)-propionic acid ethyl ester This compound was obtained by esterification of the free acid with ethanol. Boiling point 119°C / 0.16 mbar n ²⁰ _D : 1.5137 (Reference can be found in J.Chem.Soc.1929, 2014 page) (M) N-[β-(3,4-dimethoxy-phenyl)-ethyl] -3,4-Dimethoxy-phenylacetamide This compound is described in Ber.dtsch.Chem.Ges.Volume 42 (1909
obtained by the reaction of acid chloride with β-(3,4-dimethoxy-phenyl)-ethylamine in the presence of triethylamine, as described on page 1986 (N) N-[β-( 3,4-Dimethoxy-phenyl)-ethyl]-N-methyl-3,4-dimethoxy-phenylacetamide This compound is produced by methylating M with methyl iodide.A yellow oil with a refractive index n ²⁰ _D of 1.5680. Obtained as an object. (O) 3,4-dimethoxy-phenylacetic acid-
3,4-dimethoxy-benzyl ester This compound contains chloride and 3,4-dimethoxy-benzyl ester.
Obtained by reaction with benzyl alcohol. Melting point: 99-101° C. The antiseborrheic effect of the compounds used in cosmetics according to the invention was investigated in detail by the animal experiments described below. Male Wistar rats weighing 220 to 230 g were used as experimental animals. The degree of browning on the backs of rats whose backs had been pruned was visually determined.
Browning is caused by brown skin surface lipids in rats. This test shows that young female rats, as well as male rats, after washing with surfactant solutions or lipid solvents, and male rats treated whole body with estrogen, also after shearing, show only normal light pink skin. The starting point is to observe that; parallel to this, only a comparatively small amount of lipids should be extracted from the cut hair. To determine the fat suppressing effect, test substances A, B,
D, E, G and H with ethanol or ethanol/
It was applied in the form of a 1% solution in acetone (1:1) to one side on the skin of the back of 6 rats in each case. The other side was treated with only solvent without active substance (control side). A total of 1 application was made every 9 days during the 14-day test period. Other controls included a group of 6 rats that were kept completely untreated. At the end of the experiment, the back and flanks of the animals were shaved and visually inspected by a panel of judges (6 people) independently under double-blind conditions. As the first criterion, we evaluated whether the majority of judges recognized the side that processed correctly, and in doing so, we differentiated as follows:

[Table] As a second criterion, the difference between the right and left sides was evaluated, giving 1 point in each case per judge and animal, and in the following manner: 1 point for the darker side and 1 point for the darker side; A score of 0 was given to the bright side, and 0.5 to both sides in case of equality. As a third criterion, the intensity difference in brown color tone was further evaluated according to the following steps. Strong brown 3 points Medium brown 2 points Light brown 1 point No brown change 0 points A significant difference between the untreated and treated side according to the second evaluation method indicates the topical effectiveness of the substance. A third evaluation method results in a total score difference between the untreated control animals and the respective treated and untreated side of the group of experimental animals, again between the control animals and the treated side of the experimental animals. The significant difference between the two makes the action of this substance clear. In parallel to this, there should also usually be a clear difference between the untreated and treated groups of experimental animals. However, this is not always as obvious as between control animals and the treated side, which may indicate various reasons, for example mechanical mass transfer to the other side or influence of the solvent. The following diagram is used to differentiate the effects of judgment methods 2 and 3.

[Table] The following Table 1 shows the judgment results for the test substance using the above diagram.

Table Acid-oleyl ester Examples are given below for topical cosmetic preparations according to the invention for the treatment of highly fatty hair and seborrheic skin. Dermal emulsion for the treatment of fatty skin Cetylstearyl alcohol, sodium cetylstearyl sulfate and nonionic emulsifier, Emulgade F ^(R) , colloidal dispersible mixture from Dehydag 1.00 Parts by weight Cetylstearyl alcohol and nonionic emulsifier, Emulgade Fspez, ^(R) (Dehydatsug)
A mixture consisting of: 1.00 parts by weight Decyl ester of oil acid 1.00 parts by weight Stearic acid 3.00 parts by weight Wool fat, anhydrous 0.50 parts by weight Glycerin 1.00 parts by weight Triethanolamine 0.25 parts by weight Compound B 3.25 parts by weight Water 89.00 parts by weight For use on the skin in the form of an aerosol To use the emulsion, 92 parts by weight of the emulsion are charged into an aerosol container along with 8 parts by weight of propellant gas. Cream for the treatment of fatty skin Self-emulsifying mixture consisting of mono/diglycerides of higher saturated fatty acids and potassium stearate ^(R) dehydrogenase 16.0 parts by weight Cetylstearyl alcohol with about 12 moles of ethylene oxide 1.0 parts by weight 2-octyl dodeca Nol 6.0 parts by weight Isopropyl myristate 4.0 parts by weight Glycerin 6.0 parts by weight Compound D 7.0 parts by weight Water 60.0 parts by weight Shampoo for fatty hair Triethanolamine lauryl sulfate with 42% washing actives 12.0 parts by weight Coconut fatty acid diethanolamine 2.0 parts by weight Carboxymethylcellulose 0.25 parts by weight Compound E 8.25 parts by weight Perfume oil 0.2 parts by weight Water 77.3 parts by weight

Claims (1)

[Claims] 1. General formula [In the formula, R ₁ , R ₂ and R ₃ independently represent a hydrogen atom, a hydroxy group, an OR ₄ - group (in the formula, R ₄ represents an alkyl group having 1 to 6 carbon atoms) or R Two of ₁ , R ₂ and R ₃ mean a methylenedioxy group, in which case R ₁ , R ₂ and R ₃ do not mean a hydrogen atom at the same time, and X means that the carbon chain has 1 carbon atom.
~3 alkylene group, Y is CONR ₅ R ₆ or
COOR ₇ (In the formula, R ₅ and R ₆ are hydrogen atoms, alkyl groups having 1 to 6 carbon atoms, benzyru or 3,4-dimethoxybenzyl groups, and R ₇ is 1 to 6 carbon atoms.
is an alkyl group. ) means. ] or 2-(3,4-dimethoxybenzyl)-acetoacetic acid-methyl ester, 4-
(3,4-methylenedioxy-benzyloxy)-
Phenyl acetic acid ethyl ester, N-[β-(3,4
-dimethoxy-phenyl)-ethyl]-3,4-dimethoxy-phenyl-acetamide or N-[β
-(3,4-dimethoxy-phenyl)-ethyl]-
A topical cosmetic containing N-methyl-3,4-dimethoxy-phenyl-acetamide. 2 Add the compound with the above structure to 0.01% of the total amount of cosmetics.
The cosmetic composition according to claim 1, containing the cosmetic composition in an amount of ~20% by weight.